DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-33 are pending (claim set as filed on 04/27/2026).
Election/Restrictions
Applicant’s election without traverse of Group I, method claims, in the reply filed on 04/27/2026 is acknowledged.
Claims 18, 22, and 26-33 drawn to the products are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, method claims 1-17, 19-21, and 23-25 are presented for examination.
Priority
This application is a 371 of PCT/JP2021/034424, which has a foreign application to JP 2020-157646 filed on 09/18/2020.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 03/17/2023, 11/14/2025, and 02/26/2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the Examiner.
Drawings
The drawings filed on 03/17/2023 are objected to because some figures or photographs (e.g., figures 2-3, 15, et. al.) are not visually clear or illegible. Substitute figures or photographs are requested.
Abstract Objection
The abstract of the disclosure is objected to because it does not comply with the proper language and format (see MPEP 608.01(b)). Appropriate correction is required.
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as “means” and “said” should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns”, “The disclosure defined by this invention”, “The disclosure describes”, “[Object]”, or “[Solution]”.
Claim Rejections - 35 USC §112, Indefinite
The following is a quotation of 35 U.S.C. 112(b):
(B) CONCLUSION - The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 12 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 12 recites, in part, “The method according to claim 9, further comprising, in the step (c),” and therefore is rejected for lacking antecedent basis because claim 9 does not have a step (c). Appropriate correction is required.
Claim Rejections - 35 USC §102, Anticipation
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 19-21, and 23-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Takeuchi (JP 2014-136128 A - cited by the ISA and in the IDS filed on 03/17/2023).
Takeuchi’s general disclosure relates to a nerve fascicle for implantation and a method of manufacturing (see title); wherein the nerve graft bundle for transplantation that has necessary flexibility and strength and can efficiently regenerate nerves at a transplant site (see page 2: Description).
Takeuchi teaches “a nerve bundle for transplantation in which two or more microfibers containing neural stem cells or cells obtained by differentiating neural stem cells to a predetermined stage are bundled, wherein the microfibers are neural stem cells or a microgel fiber containing cells obtained by differentiating neural stem cells to a predetermined stage is coated with a high-strength hydrogel, and the two or more microgel fibers are bundled by coating with a biocompatible gel” (see abstract). Takeuchi teaches “a method of producing a nerve bundle for transplantation, a step of producing two or more microfibers in which a microgel fiber containing neural stem cells or cells obtained by differentiating neural stem cells to a predetermined stage is coated with a high strength hydrogel, and bundling the two or more microfibers and coating with a biocompatible gel or polyion complex” (see page 2).
Regarding the different cell types, Takeuchi teaches the nerve for transplantation wherein the microfiber at the center of the bundle includes nerve cells and the surrounding microfiber includes cells other than nerve cells and/or substances other than cells (see page 1). Takeuchi teaches that “it is easy to enclose different cells in each microfiber and to place microfibers containing different cells at desired positions, the degree of freedom of the structure of the nerve bundle is increased, and the nerves of the living body are increased. A configuration close to a bundle can be realized” (see page 2). Takeuchi teaches “in the step of differentiating the neural stem cells, the neural stem cells in at least some of the microfibers are differentiated into neural cells, and the neural stem cells in at least some other microfibers are differentiated into glial cells” (see page 3, 1st sentence). Takeuchi teaches “neural stem cell refers to a central nervous system such as a nerve cell, astrocyte, oligodendrocyte, Schwann cell that has the ability to proliferate and can be repeated for passage. And cells having the ability to differentiate into cells that constitute the peripheral nervous system. A neural stem cell first differentiates into a neural progenitor cell or a glial progenitor cell, the neural progenitor cell becomes a neuron (neuron), and the glial progenitor cell becomes a glial cell (a general term for cells other than the nerve cells constituting the nervous system. Including oligodendrocytes and Schwann cells)” (see page 3). Takeuchi teaches “the nerve bundle may include other types of cells and microfibers including substances other than cells. Other cells and substances other than cells are not particularly limited as long as they do not adversely affect nerve regeneration, and various stem cells, various differentiated cells (muscle cells, fibroblasts, epithelial cells, nerve cell survival, proliferation. Examples include cells that induce or retain differentiation (for example, smooth muscle cells, skeletal muscle cells, etc.), proteins, lipids, saccharides, nucleic acids, extracellular matrix, growth factors, nutrient factors, growth hormones, and the like” (see page 5). One or more types of cells may be combined (see page 6).
Takeuchi teaches “the microfiber containing neural stem cells and the like may contain components other than neural stem cells and the like. Such components include cells that induce or maintain survival, proliferation, and differentiation of nerve cells (e.g., smooth muscle cells, skeletal muscle cells, etc.), growth factors (e.g., fibroblast growth factor (FGF), epithelial cell growth factor (EGF)), trophic factors, growth hormones and the like, but are not limited to these” (see page 4).
Takeuchi teaches “the biocompatible gel is not particularly limited as long as microfibers can be bundled so as to have suitable flexibility and strength. It may be degradable, bio-absorbable or non-degradable/non-absorbable. Examples of the biocompatible gel include collagen” (see page 4).
Claim Rejections - 35 USC §103, Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 6-8 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi as applied to claims 1-5, 19-21, and 23-25 above, and in view of Fujii (US 2019/0127672 A1) - both references cited in the IDS filed on 03/17/2023.
Takeuchi’s disclosure is taught above as it pertains to a method of producing a nerve fascicle.
However, Takeuchi does not teach: preparing a substrate including at least one recess and a channel portion (claims 6-7); or in the step (a) the channel portion is covered with fibroblast before cover with the feeder cells (claim 8); or wherein the channel portion has a length of 3 mm or greater (claim 17).
Fujii’s general disclosure relates to a neuron cultivation device, a neuron cultivating method, cultivated neurons, an analysis and an identification of proteins in axon bundles, and usages of cultivated neurons (see ¶ [0001]-[0002]). A neuron cultivation device which promptly develops bundles of axons extender from neurons in vitro (see ¶ [0006], [0022]).
Fujii teaches “a method for cultivating neuron with axon, the method comprising steps of applying cultivation fluid in at least one of first chambers, at least one of second chambers, and at least one of channels connecting the first chambers and the second chambers, the first chambers, the second chambers and channels included in at least one of modules arranged in a cultivation plate; inoculating neurons in the first chambers; and cultivating the neurons, so that a bundle of axons grows and extends in each of the channels” (see ¶ [0011]-[0013], [0055]).
Fujii teaches “an aggregated neuron body consisting of a plurality of neurons with cell bodies derived from human iPS cells and axons extended from the cell bodies, the aggregated neuron body comprising: a spheroid and a bundle of axons of 1 [mm] or more in length extended from the spheroid in one direction, wherein the spheroid is an aggregation of a plurality of the cell bodies, wherein the bundle of axons is a bundle of a plurality of the axons, the bundle of axons is in a state of nonexistence of cell body to a degree that markers indicating existence of the cell bodies in Western blotting are negative” (see claim 19).
Fujii teaches “a device for cultivating neuron with axon, the device comprising: a cultivation plate; and a plurality of modules arranged in the cultivation plate, each of the modules including at least one of first chambers receivable of cell bodies of neurons, at least one of second chambers, and at least one of channels receivable of a bundle of axon extended from the cell bodies, the channels connecting the first chambers and the second chambers, wherein bottom ends of the first chambers, the second chambers and the channels axe closed and top ends of the first chambers and the second chambers are open” (see ¶ [0007]-[0010]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ or use the device such as taught by Fujii in the method of Takeuchi. The ordinary artisan would have been motivated to do so because Fujii’s neuron device allow for the cultivation of neurons so that a bundle of axons grows and extends in each of the channels to the desired lengths which would be advantageous for Takeuchi’s nerve fascicle for transplantation. The ordinary artisan would have had a reasonable expectation of success because both references are in the same field of endeavor directed to neuron cultivation and producing a nerve bundle for graft transplantation.
Regarding claim 8, Takeuchi teaches that the nerve bundle may contain other cells types including fibroblasts (see page 5). It would have been readily apparent to include fibroblasts in the channel portion of Fujii to facilitate the growth of the neurons as Takeuchi discloses other cell types may be co-cultured.
Claims 9-16 are rejected under 35 U.S.C. 103 as being unpatentable over Takeuchi in view of Fujii as applied to claims 1-8, 17, 19-21, and 23-25 above, and in further view of Temple (US 2005/0277189 A1).
The combined disclosures of Takeuchi and Fujii, herein referred to as modified-Takeuchi-Fujii, is discussed above as it pertains to a method of producing a nerve fascicle.
However, modified-Takeuchi-Fujii does not teach: feeder cells including endothelial cells (claims 9-14).
Temple’s general disclosure relates to “a method for promoting self-renewal of neural stem cells and enhancing neurogenesis. More significantly, the invention provides a method for the proliferation of a stem cell population that retains its developmental capacity to differentiate into a specific cell type” (see ¶ [0003]).
Regarding the feeder endothelial cells, Temple teaches the method comprising the steps of obtaining an original population of stem cells having a particular developmental capacity and culturing the stem cells in the presence of a trophic support, such as vascular endothelial cells or a conditioned media from a vascular endothelial cell culture, in an amount sufficient to stimulate self-renewal of the stem cells. The endothelial cells may be cultured non-contiguously from the stem cell population, that is not in contact but allowing for soluble factors produced by the endothelial cells to come into contact with the stem cells (see ¶ [0007]). Endothelial cells secrete numerous bioactive substances includes factors (e.g., VEGF, EGF, BDNF, FGF-2) that are known to affect other cell types (see ¶ [0073]). Temple teaches “to examine a possible functional interaction between neural stem cells and their vascular environment, we co-cultured neural and vascular cells (FIG. 1A). Neural stem cells from El0-11 mouse cerebral cortex were plated at clonal density on the base of culture wells, while the upper transwell compartment was seeded with purified vascular associated or other feeder cells: primary bovine pulmonary artery endothelial cells (BPAE), a mouse brain endothelial cell line (MbEND), vascular smooth muscle (VSM) cells, NIH3T3 fibroblasts” (see ¶ [0032]).
It would have been obvious to one of ordinary skill in the art to employ or use feeder endothelial cells such as taught by Temple in the method of modified-Takeuchi-Fujii. The ordinary artisan would have been motivated to do so because Temple teaches co-culturing with feeder endothelial cells promotes self-renewal of neural stem cells and enhancing neurogenesis. The ordinary artisan would have had a reasonable expectation of success because all of the cited references are drawn to the culture of neural cells.
Regarding claims 11 and 14 pertaining to endothelial cell source, the references discloses that cells may be obtained from various sources including autologous, allogeneic, or xenogeneic which are commonly employed in the art. Moreover, endothelial cells are ubiquitous throughout the body and it would have been readily apparent for one of ordinary skill in the art to envisage endothelial cells obtained from subcutaneous tissue, artery, or umbilical cord.
Regarding claims 15-16 pertaining to collagen biocompatible material, Takeuchi teaches the gel used for the microgel fiber is not particularly limited and may include collagen and different types of biocompatible gel may be coated in layers (see pages 3-4)
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-3, 6-17, and 19-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over at least claims 1-3, 5-16, and 18-20 of co-pending Application no. 17/478,271.
Although the claims at issue are not identical, they are not patentably distinct from each other because: co-pending ‘271 teaches “A method of producing a cultivated neural tissue with a first set of length and width, the method comprising culturing a neural cell population differentiated from oral mesenchymal cells on a substrate surface, wherein a portion of the surface is covered by feeder cells before culturing, wherein the portion of the surface corresponds to a second set of length and width, wherein the feeder cells promote the neural cell population to grow into a cultured basic tissue with the second set of length and width through the culturing, wherein the cultivated tissue is produced by combining a plurality of the cultured basic tissues so that the width of the cultivated tissue is larger than the width of the cultured basic tissue” (see claims 1
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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